While stroke remains the primary cause of death behind heart disease and cancer and the leading cause of serious, long-term disability in the United States (Rosamond et al 2008), decreasing incidence has been attributed to interventions including revascularization and statin therapy (Collins et al 2004). However, administration of proper treatment is limited by inadequacies in modern diagnostic technologies (Dhopra et al 2007). A variety of imaging methods are routinely employed to diagnosis peripheral atherosclerosis, including digital subtraction angiography as well as noninvasive alternatives such as magnetic resonance angiography (MRA) and duplex ultrasound. Although these imaging methods are known to be effective for detecting occlusive plaques associated with pronounced narrowing of the vessel lumen and/or blood flow obstruction, their focus on lumenal features inhibits detection of nonocclusive plaques contained in arterial walls. Furthermore, their ability to predict plaque risk for causing cerebrovascular accident (CVA) has not been well established (Raggi et al 2005). These diagnostic shortcomings result in as many as 50% of high-risk atherosclerotic plaques going undetected (Veller et al 1993), which leads to `sudden stroke'with no advanced warning of underlying disease or the ability to mitigate. On the other hand, overly aggressive plaque risk assessment in the case of stable plaques leads to unnecessary, high-risk invasive procedures that confer no additional benefit over intensive drug therapy (Golledge et al 2007). There is a clear unmet need for a validated atherosclerosis imaging modality that can improve plaque detection and predict rupture risk. To address this need, our laboratory is developing a novel, noninvasive diagnostic atherosclerosis imaging technology - Acoustic Radiation Force Impulse (ARFI) ultrasound - which exploits tissue composition by interrogating tissue material properties. Our preliminary studies show that in vivo ARFI imaging detected occlusive and nonocclusive plaques and described plaque collagen and elastin composition, which are material features relevant to predicting plaque risk (Behler et al 2006), (Behler et al 2007a), (Behler et al 2007b). The long-term goal of this research program is to develop noninvasive ARFI ultrasound for early plaque detection and identification of plaques at high risk for initiating CVA as well as cardiovascular events. The attractiveness of this line of inquiry lies not only in the potential to diminish CVD's enormous human impact by improving screening and enabling early interventions, but also in the potential to monitor existing therapies and develop new ones. As a critical first step toward achieving our long-term goal, the objectives of the proposed research are to demonstrate ARFI imaging for detecting plaques and for assessing their composition and structure in peripheral arteries. We hypothesize that in vivo, transcutaneous ARFI ultrasound is capable of detecting occlusive and nonocclusive plaques in peripheral arteries and of assessing plaque composition. ARFI plaque detection and compositional assessment may be validated in FH pig iliac arteries and in human carotid arteries. PUBLIC HEALTH RELEVANCE: Stroke is the third leading cause of death and the primary cause of serious, long-term disability in the United States. Although timely and appropriate treatment is critical to saving lives, shortcomings in conventional diagnostic imaging technologies prevent advanced warning of the disease and delay therapy. The objectives of this research proposal are to demonstrate a novel ultrasound imaging technology - Acoustic Radiation Force Impulse (ARFI) ultrasound - for improved diagnosis of atherosclerotic plaques and stroke risk.